Bladder cancer is a very common malignancy: it is the sixth most common cancer in the US. In 2012, there were an estimated 73 510 new cases of bladder cancer and 14 880 bladder cancer-related deaths in the United States.
According to the American Cancer Society, in 2014, the risk men will develop this cancer during their life is about 1 in 26 and 1 in 90 for women. It is considered as an elderly disease: 9 on 10 of the people touched by bladder cancer are over 55 years old. The main risk factors are smoking, chemical exposures (for instance to products used in the textile dye industry), genetic predisposition and certain medical treatment (as chemotherapy). Bladder cancer tends to recur and a patient needs a life-long close follow-up.
Bladder cancer can be divided into muscle invasive bladder cancer and non-muscle invasive bladder cancer (NMIBC). More than 70% of patients have NMIBC (Babjuk M. et al. (2011), Eur. Urol. 59: 997-1008). The recurrence rates of NMIBC range from 50% to 70%, and disease progression to muscle invasion over a 5-year period from 10 to 15% (Babjuk et al. (2013), Eur Urol. 64(4):639-53). Different classifications for risk of recurrence or progression have been proposed, based on the characteristics of the tumor itself (number, volume, invasion, grade). The EORTC risk tables for patient with stage Ta TI bladder cancer are the most widely used (Sylvester et al. (2006), Eur. Urol. 49: 466-477).
However from external validation analysis data, this risk tables exhibit a poor discrimination for both disease recurrence and progression in NMIBC patients. In particular, this model overestimates the risk of disease recurrence and progression in high-risk patients (Xylinas et al. (2013), Urol. Oncol. 31(1):99-103).
Thus, first, there is a need to find more accurate and enhanced methods, which would be quick and cost effective, for the prognosis of the outcome of a patient afflicted by a cancer, preferably bladder cancer, and for the monitoring of said cancer, preferably bladder cancer, particularly non-muscle invasive bladder cancer.
Second, the treatment used to treat bladder cancer depends on the type of cancer (whether it is muscle-invasive or not) and on the grade of the tumor.
Patients with muscle invasive bladder cancer are usually treated by chemotherapy and radical cystectomy or radiotherapy (Sauer et al. (1998), Int J Radiat Oncol Biol Phys., 40(1): 121-7).
The main treatments used in NMIBC are transurethral resection (TUR) and intravesical instillation with a chemotherapeutic agent or with Bacillus Calmette-Guerin (BCG) (van Rhijn et al. (2009), Eur. Urol. 56:430-442)
TUR is a surgical procedure and is also used in the diagnosis and prognosis of bladder cancer. Its goal is to observe and remove the tumor by passing a cystoscope through the urethra. Intravesical instillation consists in direct introduction of a chemotherapeutic agent or of BCG into the bladder through a catheter. Several analyses demonstrated that BCG is more effective than chemotherapy for reducing the recurrence and progression of bladder cancer, but it is more toxic (Bohle et al. (2003), J Urol. 169:90-5). The introduction of BCG via intravesical instillation produces a lot of side effects among which are infectious reactions, allergic reactions and auto-immune reactions due to the introduction of living bacteria into the bladder (Neuzillet et al. (2012), Progres en urologie, 22:989-998).
Those treatments are quite heavy to support and inconvenient for the patient. Moreover, treatment with BCG is the last option before bladder ablation.
Thus there is still a need to find more secure and bearable treatments in bladder cancer, and more particularly, there is a need to delay treatment with BCG as long as possible, so as to avoid the irreversible surgery.